Relevance of nuclear receptor expression in a Tchreg cell line, HOZOT: RXRα and PPARγ negatively regulate IFN-γ production

Abstract

Nuclear receptors (NRs) have recently received much attention for their newly discovered roles in T cell development, as exemplified by RARα (Treg cells) and RORγt (Th17 cells). In previous studies, we characterized a new type of T cell subset, designated as Tchreg (cytotoxic, helper, and regulatory T) cells, in terms of its cytokine signature. In this study, we investigated the expression and functional relevance of NRs in Tchreg cells by performing mRNA profiling of HOZOT, a cord blood-derived Tchreg cell line. We identified eleven inducible and eight constitutively expressed NRs in HOZOT. Among these NRs, RXRα and PPARγ showed features of signature NRs of Tchreg cells because they were selectively expressed in HOZOT compared with other T cell subsets. These NRs exhibited contrasting expression patterns, as RXRα was independent of anti-CD3/28 antibody stimulation while PPARγ was stimulated-dependent. Upon agonist treatment, both proteins translocated to the nucleus and inhibited IFN-γ production through binding to the promoter region of the IFN-γ gene. These results provide new insight into the roles of RXRα and PPARγ in T cell biology, especially in their biological relevance in Tchreg cells.